High fat diet causes thickening of the arteries up to the cellular level

Atherosclerosis is a difficult problem: the arteries become thicker and stiffer, which can lead to heart disease and strokes, but it is unclear exactly how cholesterol causes this thickening. Cholesterol is a small fat molecule that circulates in our blood with the help of lipoproteins. High levels of low-density lipoprotein (LDL) in the blood is a key risk factor for atherosclerosis. And a variant of LDL, called oxidized LDL, can also contribute to arterial plaques. Manuela Ayee, who worked with Irena Levitan at the University of Illinois, will present her research on how these two LDLs cause a thickening at the cellular level at the 63rd Annual Biophysical Society Congress, to be held March 2 to 6, 2019 in Baltimore, Maryland. .

Cholesterol is not quite bad, it's an essential fat that cells need to make membranes and steroid hormones. When it is transported in our body, it needs a lipoprotein transporter. LDLs carry cholesterol cells away from the liver and high density lipoproteins (HDL) return cholesterol to the liver. LDL has long been thought to be the cause of atherosclerosis, but recent evidence suggests that oxidized LDL is also a key player. Ayee and Levitan wanted to know if it was either of these LDLs that was the main problem.

Ayee and Levitan fed mice with a well-balanced normal diet or a "Western fat-rich diet" designed to reflect the levels of fat, protein and carbohydrate typically found in fast food menus. They observed that the mice consuming the latter diet rapidly developed stiffer arteries, up to the endothelial cell layer surrounding the blood vessels. They measured the levels of oxidized LDL and LDL in these mice in order to be able to apply the same concentrations to human endothelial cells in culture, and then performed precise measurements using atomic force microscopy of membrane tension and stiffness. cytoskeleton.

In culture, compared to cells without added lipoproteins, physiological levels of oxidized LDL and LDL caused thickening of the cell membrane and increased tension when added individually, which amplified the change.

"To our surprise, a very small amount of oxidized LDL radically changes the structure of the cell membrane," said Ayee.

Their results suggest that changes in dietary blood lipid levels may fundamentally disrupt the integrity of the endothelial cell layer.

"We believe that changes in the cell membrane can allow the processes involved in atherosclerosis to begin," Ayee concluded.

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Provided by
Biophysical Society